Brandeis M, Frank D, Keshet I, Siegfried Z, Mendelsohn M, Nemes A, Temper V, Razin A, Cedar H
Department of Cellular Biochemistry, Hebrew University Medical School, Jerusalem, Israel.
Nature. 1994 Sep 29;371(6496):435-8. doi: 10.1038/371435a0.
Animal somatic cell DNA is characterized by a bimodal pattern of methylation: tissue-specific genes are methylated in most cell types whereas housekeeping genes have 5' CpG islands which are constitutively unmethylated. Because methyl moieties derived from the gametes are erased in the morula and early blastula, this profile must be re-established in every generation; this is apparently accomplished by a wave of non-CpG island de novo methylation that occurs at implantation. Using transfection into embryonic stem cells and transgenic mice as a model system, we now show that Sp1 elements play a key role in protecting a CpG island in the adenine phosphoribosyltransferase (APRT) gene from de novo methylation. This recognition mechanism represents a critical step in embryogenesis, as it is responsible for setting up the correct genome methylation pattern which, in turn, is involved in regulating basal gene expression in the organism.
动物体细胞DNA的特征是具有双峰甲基化模式：组织特异性基因在大多数细胞类型中发生甲基化，而管家基因具有5' CpG岛，这些岛组成性地保持未甲基化状态。由于来自配子的甲基部分在桑椹胚和早期囊胚中被清除，因此这种模式必须在每一代中重新建立；这显然是通过植入时发生的一波非CpG岛从头甲基化来实现的。利用转染胚胎干细胞和转基因小鼠作为模型系统，我们现在表明，Sp1元件在保护腺嘌呤磷酸核糖转移酶（APRT）基因中的一个CpG岛免受从头甲基化方面发挥关键作用。这种识别机制代表了胚胎发育中的一个关键步骤，因为它负责建立正确的基因组甲基化模式，而这反过来又参与调节生物体中的基础基因表达。
